Search Results (22,395)

Cellular senescence is closely connected with cancer progression, recurrence, and metastasis. Senotherapy aims to soothe the harmful effects of senescent cells either by inducing their apoptosis (senolytic) or by suppressing the senescence-associated secretory phenotype (SASP) (senomorphic). Fisetin, a well-studied senotherapeutic drug, was selected for this study to evaluate its efficiency when delivered in a liposomal formulation. The experiment evaluated the impact of liposome-encapsulated fisetin on senescent cells induced by doxorubicin (DOX) from two cell lines: WI-38 (normal lung fibroblasts) and A549 (lung carcinoma). Senescence was characterized by SA-β-galactosidase (SA-β-gal) activity, proliferation, morphology, and secretion of pro-inflammatory interleukin 6 (IL-6) and interleukin 8 (IL-8). Due to fisetin’s hydrophobic nature, it was encapsulated in liposomes to enhance cellular delivery. Cellular uptake studies confirmed that the liposomes were effectively internalized by both senescent cell types. Treatment with fisetin-loaded liposomes revealed a lack of senolytic effects but showed senomorphic activity, as evidenced by a significant reduction in IL-6 and IL-8 secretion in senescent cells. The liposomal formulation enhanced fisetin’s therapeutic efficacy, showing comparable results even at the lowest tested concentration. Full article

Accurate forecasting of tropical cyclone (TC) tracks is critical for disaster preparedness and risk mitigation. While traditional numerical weather prediction (NWP) systems have long served as the backbone of operational forecasting, they face limitations in computational cost and sensitivity to initial conditions. In recent years, deep learning (DL) has emerged as a promising alternative, offering data-driven modeling capabilities for capturing nonlinear spatiotemporal patterns. This paper presents a comprehensive review of DL-based approaches for TC track forecasting. We categorize all DL-based TC tracking models according to the architecture, including recurrent neural networks (RNNs), convolutional neural networks (CNNs), Transformers, graph neural networks (GNNs), generative models, and Fourier-based operators. To enable rigorous performance comparison, we introduce a Unified Geodesic Distance Error (UGDE) metric that standardizes evaluation across diverse studies and lead times. Based on this metric, we conduct a critical comparison of state-of-the-art models and identify key insights into their relative strengths, limitations, and suitable application scenarios. Building on this framework, we conduct a critical cross-model analysis that reveals key trends, performance disparities, and architectural tradeoffs. Our analysis also highlights several persistent challenges, such as long-term forecast degradation, limited physical integration, and generalization to extreme events, pointing toward future directions for developing more robust and operationally viable DL models for TC track forecasting. To support reproducibility and facilitate standardized evaluation, we release an open-source UGDE conversion tool on GitHub. Full article

Background: The influence of the initial ablation modality on pulmonary vein (PV) reconnection and substrate characteristics in redo procedures for recurrent atrial fibrillation (AF) remains unclear. We assessed how different thermal strategies—ablation index (AI)-guided radiofrequency (RF) versus cryoballoon (CB) ablation—affect remapping findings during redo pulmonary vein isolation (PVI). Methods: We included patients undergoing redo ablation between 2015 and 2024 with high-density electroanatomic mapping. Initial PVI modalities were retrospectively classified as low-power, long-duration (LPLD) RF; high-power, short-duration (HPSD) RF; or second-/third-generation CB. Reconnection sites were mapped using multielectrode catheters. Redo PVI was performed using AI-guided RF. Segments showing PV reconnection were reisolated; if all PVs remained isolated and AF persisted, posterior wall isolation was performed. Results: Among 195 patients (LPLD: 63; HPSD: 30; CB: 102), complete PVI at redo was observed in 0% (LPLD), 23.3% (HPSD), and 10.1% (CB) (p < 0.01 for LPLD vs. HPSD). Reconnection patterns varied by technique; LPLD primarily affected the right carina, while HPSD and CB showed reconnections at the LSPV ridge. Organized atrial tachycardia was least frequent after CB (12.7%, p < 0.002). Conclusion: Initial ablation strategy significantly influences PV reconnection and post-PVI arrhythmia patterns, with implications for redo procedure planning. Full article

Background/Objectives: Preoperative strategies for hepatocellular carcinoma (HCC) requiring major hepatectomy remain controversial, particularly in “borderline resectable” cases. This study aimed to evaluate the oncological benefit and perioperative safety of Yttrium-90 transarterial radioembolization (TARE) in patients undergoing right or extended right hepatectomy for HCC. Material and Methods: All consecutive patients who underwent right or extended right hepatectomy for HCC at a single tertiary center between January 2013 and December 2023 were retrospectively reviewed. Patients were grouped based on whether they received preoperative TARE or underwent upfront resection. Outcomes analyzed included perioperative morbidity and long-term oncological endpoints. Results: A total of 39 patients were included, of whom 18 received preoperative TARE and 21 underwent upfront surgery. Patients in the TARE group showed significantly greater tumor necrosis at pathology (70% vs. 10%, p = 0.002) and more frequent extended resections. Five-year cancer-specific survival (80.4% vs. 33.5%, p = 0.011), recurrence-free survival (33.8% vs. 14.0%, p = 0.047), and curative-intent disease-free survival (69.3% vs. 18.9%, p = 0.0037) were significantly higher in the TARE group. Overall survival showed a favorable trend. Intraoperative outcomes, postoperative morbidity, and 90-day mortality were comparable between groups. Conclusions: Preoperative TARE is a safe and effective neoadjuvant strategy in selected patients with HCC undergoing major hepatectomy. It may enhance long-term oncological outcomes without increasing surgical risk, supporting its potential role in the management of borderline resectable HCC. Full article

Rural roads are critical for connecting isolated communities to essential services such as education and health and administrative services, as well as production and market opportunities in low-income countries. More than 70% of movements of people and goods in Sub-Saharan Africa are heavily reliant on rural transport systems, using both motorised but mainly alternative means of transport. However, rural roads often suffer from poor construction due to the use of low-strength, in situ soils and limited financial resources, leading to premature failures and subsequent traffic disruptions with significant economic losses. This study investigates the use of rice husk ash (RHA), a waste byproduct from rice production, as a sustainable supplement to Ordinary Portland Cement (OPC) for soil stabilisation in order to increase durability and sustainability of rural roads, hence limit recurrent maintenance needs and associated transport costs and challenges. To conduct this study, soil samples collected from Mulungushi, Zambia, were treated with combinations of 6–10% OPC and 10–15% RHA by weight. Laboratory tests measured maximum dry density (MDD), optimum moisture content (OMC), and California Bearing Ratio (CBR) values; the main parameters assessed to ensure the quality of road construction soils. Results showed that while the MDD did not change significantly and varied between 1505 kg/m³ and 1519 kg/m³, the OMC increased hugely from 19.6% to as high as 26.2% after treatment with RHA. The CBR value improved significantly, with the 8% OPC + 10% RHA mixture achieving the highest resistance to deformation. These results suggest that RHA can enhance the durability and sustainability of rural roads and hence improve transport systems and subsequently improve socioeconomic factors in rural areas. Full article

Gastric-type cervical adenocarcinoma (GCA) is a rare and aggressive subtype of cervical adenocarcinoma. Despite its clinical significance, its molecular carcinogenesis and therapeutic targets remain poorly understood. This study aimed to compare the clinicopathological, immunohistochemical, and molecular profiles of GCA and usual-type cervical adenocarcinoma (UCA), exploring prognostic and therapeutic biomarkers in a Japanese population. A total of 110 cervical adenocarcinoma cases, including 16 GCA and 94 UCA cases, were retrospectively analyzed for clinicopathological features, and a panel of immunohistochemical markers was assessed. Sanger sequences were performed for the KRAS, PIK3CA, and BRAF genes, and survival and clinicopathological correlations were assessed using Kaplan–Meier and Cox regression analyses. GCA was significantly associated with more aggressive features than UCA, including lymph node involvement, advanced FIGO stages, increasing recurrence rate, and poor survival status. High ARID1B expression was observed in a subset of GCA cases and correlated with worse progression-free and overall survival. Additionally, PD-L1 expression was more frequent in GCA than UCA and was associated with unfavorable prognostic factors. Conversely, UCA cases showed strong p16 expression, supporting their HPV-driven pathogenesis. Molecular profiling revealed KRAS and PIK3CA mutations in both subtypes, while BRAF mutations were identified exclusively in GCA. These findings reveal distinct clinical and molecular profiles for both tumor types and underscore ARID1B and PD-L1 as predictive prognostic and therapeutic biomarkers in GCA, implicating the use of subtype-specific treatment strategies. Full article

Pelvic organ prolapse (POP) is a prevalent condition, affecting women all over the world, and is commonly treated through surgical interventions that present limitations such as recurrence or complications associated with synthetic meshes. In this study, biodegradable poly($ϵ$-caprolactone) (PCL) cog threads are proposed as a minimally invasive alternative for vaginal wall reinforcement. A custom cutting tool was developed to fabricate threads with varying barb angles (90°, 75°, 60°, and 45°), which were produced via Melt Electrowriting. Their mechanical behavior was assessed through uniaxial tensile tests and validated using finite element simulations. The results showed that barb orientation had minimal influence on tensile performance. In simulations of anterior vaginal wall deformation under cough pressure, all cog thread configurations significantly reduced displacement in the damaged tissue model, achieving values comparable to or even lower than those of healthy tissue. A ball burst simulation using an anatomically accurate model further demonstrated a 13% increase in reaction force with cog thread reinforcement. Despite fabrication limitations, this study supports the biomechanical potential of 3D-printed PCL cog threads for POP treatment, and lays the groundwork for future in vivo validation. Full article

Background and Objectives: Extramedullary plasmacytoma (EMP) is a rare monoclonal B-cell neoplasm that typically affects the head and neck region, with a predilection for the sinonasal tract. Clinical presentation is often nonspecific, leading to delayed diagnosis. This study aims to improve our understanding of sinonasal EMP by reviewing the recent literature and presenting a case series from our clinical experience. Materials and Methods: A systematic review of published cases of sinonasal EMP from 2000 to 2023 was conducted using the PubMed database, yielding 28 eligible cases. Additionally, we retrospectively analyzed three patients diagnosed and treated at our institutions. Inclusion criteria included histologically and immunohistochemically confirmed EMP without evidence of systemic multiple myeloma. Data on demographics, tumor location, symptoms, treatment, and outcomes were collected and analyzed descriptively. Results: Sinonasal EMP most commonly presented with unilateral nasal obstruction and epistaxis. Tumors were primarily located in the nasal cavity and paranasal sinuses, often extending beyond a single anatomical site. In the literature cohort, the most frequent treatment was combined surgery and radiotherapy (35.71%), followed by radiotherapy alone (17.86%). Recurrence was reported in 10.71% of cases, and 7.14% of patients died due to disease progression. All three patients in our case series underwent surgical excision; two received postoperative radiotherapy. No recurrences or progression to multiple myeloma were observed during follow-up (12–24 months). Conclusions: Sinonasal EMP is a rare but radiosensitive tumor with a favorable prognosis when treated with surgery and/or radiotherapy. Early diagnosis, histopathological confirmation, and exclusion of systemic disease are essential. Multidisciplinary management and long-term follow-up are critical due to the risk of recurrence and transformation into multiple myeloma. Full article

Coarse-grained soils serve as essential fill materials in earth–rock dam engineering, where their mechanical properties critically influence dam deformation and stability, directly impacting project safety. Artificial intelligence (AI) techniques are emerging as powerful tools for predicting the mechanical properties of coarse-grained soils. However, AI-based prediction models for these properties face persistent challenges, particularly in parameter tuning—a process requiring substantial computational resources, extensive time, and specialized expertise. To address these limitations, this study proposes a novel prediction model that integrates Adaptive Simulated Annealing (ASA) with an improved Particle Swarm Optimization (PSO) algorithm to optimize the Elman Neural Network (ENN). The methodology encompasses three key aspects: First, the standard PSO algorithm is enhanced by dynamically adjusting its inertial weight and learning factors. The ASA algorithm is then employed to optimize the Adaptive PSO (APSO), effectively mitigating premature convergence and local optima entrapment during training, thereby ensuring convergence to the global optimum. Second, the refined PSO algorithm optimizes the ENN, overcoming its inherent limitations of slow convergence and susceptibility to local minima. Finally, validation through real-world engineering case studies demonstrates that the ASA-PSO-optimized ENN model achieves high accuracy in predicting the mechanical properties of coarse-grained soils. This model provides reliable constitutive parameters for stress–strain analysis in earth–rock dam engineering applications. Full article

Background/Objectives: Pulmonary vein isolation (PVI) via cryoballoon ablation (CBA) is a recommended therapeutic strategy for patients with symptomatic paroxysmal and persistent atrial fibrillation (AF) who are refractory to antiarrhythmic drugs. Although PVI has demonstrated efficacy in reducing AF recurrence and improving patients’ quality of life, its impact on respiratory function is not well understood, particularly in patients with comorbid conditions. The aim of the study was to search for functional predictors of the respiratory system in the process of evaluating the efficiency of clinical assessment of CBA in patients with AF. Methods: We conducted a prospective study on 42 patients with symptomatic AF who underwent CBA, assessing their respiratory function through spirometry before and 30 days after the procedure. Exclusion criteria included pre-existing lung disease and cardiac insufficiency. The impact of variables such as body mass index (BMI), coronary artery disease (CAD) and heart failure (HF) on spirometry parameters was analyzed using statistical tests. Results: No significant changes were observed in overall post-PVI spirometry parameters for the full cohort. However, post hoc analyses revealed a significant decline in ΔMEF₇₅ in patients with CAD and BMI ≥ 30 kg/m², whereas ΔFEV₁/FVCex was significantly increased in patients with HF, as well as in patients with ejection fraction (EF) < 50%. Conclusions: CBA for AF does not universally affect respiratory function in the short term, but specific subgroups, including patients with CAD and a higher BMI, may require post-procedure respiratory monitoring. In addition, PVI may improve lung function in patients with HF and reduced EF. Full article

Background/Objectives: Cancer suffers from unresolved therapeutic challenges owing to the lack of targeted therapies and heightened recurrence risk. This study aimed to investigate the new series of hydroxamate by structurally modifying the pharmacophore of vorinostat. Methods: The present work involves the synthesis of 15 differently substituted 2H-1,2,3-triazole-based hydroxamide analogs by employing triazole ring as a cap with varied linker fragments. The compounds were evaluated for their anticancer effect, especially their anti-breast cancer response. Molecular docking and molecular dynamics simulations were conducted to examine binding interactions. Results: Results indicated that among all synthesized hybrids, the molecule VI(i) inhibits the growth of MCF-7 and A-549 cells (GI₅₀ < 10 μg/mL) in an antiproliferative assay. Compound VI(i) was also tested for cytotoxic activity by employing an MTT assay against A549, MCF-7, and MDA-MB-231 cell lines, and the findings indicate its potent anticancer response, especially against MCF-7 cells with IC₅₀ of 60 µg/mL. However, it experiences minimal toxicity towards the normal cell line (HEK-293). Mechanistic studies revealed a dual-pathway activation: first, apoptosis (17.18% of early and 10.22% of late apoptotic cells by annexin V/PI analysis); second, cell cycle arrest at the S and G2/M phases. It also promotes ROS generation in a concentration-dependent manner. The HDAC–inhibitory assay, extended in silico molecular docking, and MD simulation experiments further validated its significant binding affinity towards HDAC 1 and 6 isoforms. DFT and ADMET screening further support the biological proclivity of the title compounds. The notable biological contribution of VI(i) highlights it as a potential candidate, especially against breast cancer cells. Full article

Multimodal sentiment analysis (MSA) faces key challenges such as incomplete modality inputs, long-range temporal dependencies, and suboptimal fusion strategies. To address these, we propose MGMR-Net, a Mamba-guided multimodal reconstruction and fusion network that integrates modality-aware reconstruction with text-centric fusion within an efficient state-space modeling framework. MGMR-Net consists of two core components: the Mamba-collaborative fusion module, which utilizes a two-stage selective state-space mechanism for fine-grained cross-modal alignment and hierarchical temporal integration, and the Mamba-enhanced reconstruction module, which employs continuous-time recurrence and dynamic gating to accurately recover corrupted or missing modality features. The entire network is jointly optimized via a unified multi-task loss, enabling simultaneous learning of discriminative features for sentiment prediction and reconstructive features for modality recovery. Extensive experiments on CMU-MOSI, CMU-MOSEI, and CH-SIMS datasets demonstrate that MGMR-Net consistently outperforms several baseline methods under both complete and missing modality settings, achieving superior accuracy, robustness, and generalization. Full article

Nasal irrigation (NI) is an effective, safe, low-cost strategy for treating and preventing upper respiratory tract diseases. High-volume, low-pressure saline irrigations are the most efficient method for removing infectious agents, allergens, and inflammatory mediators. This article reviews clinical evidence supporting NI use in various conditions: nasal congestion in infants, recurrent respiratory infections, acute and chronic rhinosinusitis, allergic and gestational rhinitis, empty nose syndrome, and post-endoscopic sinus surgery care. NI improves symptoms, reduces recurrence, enhances the efficacy of topical drugs, and decreases the need for antibiotics and decongestants. During the COVID-19 pandemic, NI has also been explored as a complementary measure to reduce viral load. Due to the safe profile and mechanical cleansing action on inflammatory mucus, nasal irrigations represent a valuable adjunctive treatment across a wide range of sinonasal conditions. Full article

Background and Clinical Significance: Angioleiomyoma (ALM) is a benign tumor that generally presents as a single lesion and, according to the updated WHO classification, includes the following three histological subtypes: solid (or capillary), cavernous, and venous. Typically, ALMs are described as well-defined nodules in the lower extremities but are unusually located in the acral locations and toes. We summarize two cases of ALM and perform a systematic review to provide foot surgeons with the most up-to-date and useful information on the epidemiological aspects, anatomical distribution, and specific histological subtypes of ALM in the foot. Materials and Methods: A systematic review was carried out according to the criteria of a PICO framework, and a systematic search and data processing were carried out according to the PRISMA guidelines. We analyzed patient demographics, clinical characteristics, diagnostic workup, treatment, and clinical outcomes. Each one of the included articles was independently assessed for methodological quality and risk of bias by an independent evaluator. The risk of bias of the included studies was assessed based on their characteristics. Results: This systematic review included 14 case series with 172 reported cases of ALM. One hundred and seventy-two (18.57%) were cases of ALM located on foot, excluding the ankle region. The female-to-male ratio was 1.48. The most common location was the hindfoot (41.5%), followed by the forefoot (20.2%) and the midfoot (8.9%). In 29.4% of cases, the location of the lesions could not be determined. The most frequent location of the lesions was subcutaneous (69%), followed by subaponeurotic (16.5%) and skin (14.5%) locations. The most frequent histological presentation was the solid histologic subtype (65%), followed by the venous subtype (21%) and the cavernous subtype (14%), respectively. Of the total reported cases of ALM located in foot, 63.1% presented as solid painful lesions. Calcified presentations occurred in 7% of cases, with more than half of the cases located in the hindfoot. Surgical excision was the treatment of choice in the two herein reported cases of solid ALM located in the hindfoot, one of them with a calcified presentation. No recurrence was observed in either case after two and five years of follow-up, respectively. All cases reviewed after surgical excision showed a low recurrence rate with a favorable prognosis regardless of the histological subtype and a very rare tendency toward malignancy. Conclusions: ALMs of the foot present as well-defined, painful nodules in the subcutaneous tissue of middle-aged women. Solid histological subtypes are the most prevalent. Histopathological analysis is usually essential for confirmation. Treatment consists primarily of direct excision, with remarkably low recurrence rates. Full article

Background/Objectives: Bladder cancer is a common malignancy with a high rate of recurrence and progression. Recent studies have identified that the urinary microbiome can be a key factor in tumor pathogenesis, progression, and outcomes. This narrative review is designed to summarize current evidence regarding the urobiome and explore its diagnostic and therapeutic potential. Methods: Studies between 2019 and 2024 were identified through the PubMed/MEDLINE and Google Scholar databases. Case reports and non-English-language articles were excluded. Results: The main findings revealed that specific bacteria, viruses, and taxa are linked to bladder cancer presence, progression, and response to immunotherapy treatment. Urinary microbiota differ by tumor type, sex, smoking status, and occupational exposure to toxins. Conclusions: Urinary microbiome and certain types of viruses present in urine may serve as promising tools to enhance bladder cancer diagnosis and predict treatment response. However, larger longitudinal studies are needed to confirm and establish these findings. Furthermore, integration of the urinary microbiome in clinical practice and public health strategies may reduce disease-related burden. Full article